Mechanism Of Action
XEPI is an antimicrobial drug [see
The exposure response relationship for
ozenoxacin following topical application has not been studied, however; a
relationship is unlikely because systemic exposure following topical
application is negligible [see Pharmacokinetics].
Four pharmacokinetic studies were
conducted in 110 patients utilizing varying strengths of ozenoxacin cream, up
to 2% (twice the concentration of the marketed formulation). Three of these
studies assessed systemic absorption in healthy subjects and in subjects with
impetigo. These studies were conducted with either single or repeated
application of up to 1 g ozenoxacin cream to intact or abraded skin (up to 200
cm² surface area). No systemic absorption was
observed in 84 of 86 subjects, and negligible systemic absorpÂtion was observed
at the level of detection (0.489 ng/mL) in 2 subjects.
Plasma protein binding of [14C]-ozenoxacin was moderate (~80 to 85%) and did not appear
to be dependent on concentration. Since negligible systemic absorption was
observed in clinical studies, tissue distribution has not been investigated in
Ozenoxacin was not metabolized in the
presence of fresh human skin discs and was minimally metabolized in human
Studies have not been investigated in
humans due to the negligible systemic absorption observed in clinical studies.
Mechanism Of Action
Ozenoxacin is a quinolone antimicrobial
drug. The mechanism of action involves the inhiÂbition of bacterial DNA
replication enzymes, DNA gyrase A and topoisomerase IV. OzenoxaÂcin has been
shown to be bactericidal against S. aureus and S. pyogenes organisms.
The mechanism of quinolone resistance can
arise through mutations of one or more of the genes that encode DNA gyrase or
topoisomerase IV. Resistant organisms will typically carry a combination of
mutations within gyrA and parC subunits.
Overall the frequency of resistant mutants
selected by ozenoxacin is ≤10-10.
Interaction With Other Antimicrobials
Ozenoxacin has been tested in combination
with 17 other commonly used antimicrobial agents against S. aureus and S.pyogenes.
Antagonism interactions with ozenoxacin were observed with ciprofloxacin
against S. aureus.
Ozenoxacin has been shown to be active
against most isolates of the following microorÂganisms, both in vitro and in
clinical infections [see INDICATIONS AND USAGE]:
Staphylococcus aureus (including methicillin-resistant isolates)
The safety and efficacy of XEPI for the
treatment of impetigo was evaluated in two multi-center, randomized,
double-blind placebo controlled clinical trials (Trial 1, (NCT01397461) and
Trial 2, (NCT02090764)). Seven-hundred twenty-three (723) subjects two months
of age and older with an affected body surface area of up to 100 cm², and not exceeding 2% for subjects aged 2 months to 11
years were randomized to XEPI or placebo. Subjects applied XEPI or placebo
twice daily for 5 days. Subjects with underlying skin disease (e.g.,
preexisting eczematous dermatitis), skin trauma, clinical evidence of secondary
infection, or systemic signs and symptoms of infection (such as fever), were
excluded from these studies.
Overall clinical success was defined as no
need for additional antimicrobial therapy of the baseline affected area(s) and
absence/reduction in clinical signs and symptoms assessed at the end of therapy
(Day 6-7), as follows: absence of exudates/pus, crusting, tissue warmth, and
pain; and erythema/inflammation, tissue edema, and itching assessed as less
than mild in Trial 1; and absence of blistering, exudates/pus, crusting, and
itching/pain, and mild or improved erythema/inflammation in Trial 2. Table 2
below presents the results for clinical response at the end of therapy.
Table 2 : Clinical Response at End of Therapy in Trial 1 and
Trial 2 in All Randomized Subjects
(N = 155) n (%)
(N = 156) n (%)
(N = 206) n (%)
(N = 206) n (%)
|Unable to determine
|a The success rates for ozenoxacin were
significantly different than placebo in Study 1 and Study 2 (p = 0.002 and p =
The most commonly identified bacteria were S. aureus
and S. pyogenes. Table 3 below presents the results for clinical success
at end of therapy in subjects with S.aureus or S.pyogenes at
Table 3 : Clinical Success at End of Therapy in Trial
1 and Trial 2 in Subjects with S. aureus or S. pyogenes